Yellow Fever

  • Medical Author:
    Steven Doerr, MD

    Steven Doerr, MD, is a U.S. board-certified Emergency Medicine Physician. Dr. Doerr received his undergraduate degree in Spanish from the University of Colorado at Boulder. He graduated with his Medical Degree from the University Of Colorado Health Sciences Center in Denver, Colorado in 1998 and completed his residency training in Emergency Medicine from Denver Health Medical Center in Denver, Colorado in 2002, where he also served as Chief Resident.

  • Medical Editor: Jerry R. Balentine, DO, FACEP
    Jerry R. Balentine, DO, FACEP

    Jerry R. Balentine, DO, FACEP

    Dr. Balentine received his undergraduate degree from McDaniel College in Westminster, Maryland. He attended medical school at the Philadelphia College of Osteopathic Medicine graduating in1983. He completed his internship at St. Joseph's Hospital in Philadelphia and his Emergency Medicine residency at Lincoln Medical and Mental Health Center in the Bronx, where he served as chief resident.

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Yellow fever facts

  • Yellow fever is an infectious disease caused by the yellow fever virus.
  • Yellow fever is transmitted to humans by the bite of infected mosquitoes.
  • Yellow fever is endemic in areas of Africa and South America.
  • The symptoms of yellow fever include fever, headache, and muscle aches, with some patients going on to develop life-threatening complications.
  • Yellow fever is diagnosed clinically, with laboratory confirmatory testing available.
  • The treatment for yellow fever is supportive.
  • Yellow fever can be prevented by vaccination and mosquito-control measures.

What is yellow fever? What is the history of yellow fever?

Yellow fever is an acute viral infectious disease that is transmitted to humans through the bite of infected mosquitoes. Though many cases of yellow fever are mild and self-limiting, yellow fever can also be a life-threatening disease causing hemorrhagic fever and hepatitis (hence the term "yellow" from the jaundice it can cause). This viral disease occurs in tropical areas of Africa and South America, and each year there are an estimated 200,000 cases of yellow fever worldwide, leading to approximately 30,000 deaths. An increase in the number of cases of yellow fever in the last few decades has led to campaigns aimed at improving public awareness and disease prevention for this re-emerging infectious disease.

Yellow fever is thought to have originated in Africa and was likely brought to the Americas on ships during the slave trade. Several significant yellow fever outbreaks have occurred throughout history, with the first documented outbreak occurring in the Yucatan peninsula during the 17th century. During the late 18th century, a severe yellow fever outbreak struck New England and several North American port cities. The city of Philadelphia is thought to have lost about one-tenth of its population during the 1793 yellow fever epidemic, causing many notable figures in American politics to flee the city. The last major yellow fever outbreak in North America occurred in New Orleans in 1905.

The theory that yellow fever is transmitted by a mosquito was first introduced by a Cuban physician, Dr. Carlos Finlay, in the late 19th century. It was not until 1900, using earlier research from Dr. Finlay as a foundation, that U.S. Army Major Dr. Walter Reed and his team proved that yellow fever was in fact transmitted by mosquitoes. This groundbreaking idea was instrumental in leading to the subsequent control of yellow fever in various regions. The virus responsible for yellow fever was later isolated in the late 1920s, and this breakthrough discovery allowed Max Theiler to later develop the first vaccine against yellow fever in the 1930s. This successful vaccine helped control and eliminate yellow fever from various countries in Africa and South America during the mid-20th century.

This picture shows multiple 
virions of the yellow fever virus.
This picture shows multiple virions of the yellow fever virus. Source: CDC

Quick Guide25 Ways to Stay Well Abroad in Pictures

25 Ways to Stay Well Abroad in Pictures

Yellow Fever Vaccination

Do you need vaccinations before traveling abroad?

Travelers to other countries often face health issues they wouldn't ordinarily experience at home. To minimize your risks of becoming seriously ill when traveling abroad, you should find out in advance whether any specific immunizations may be recommended for travel to the region of the world you'll be visiting. It's also a good time to review your own immunization history.

What causes yellow fever?

Yellow fever is caused by a virus. The yellow fever virus is a single-stranded RNA virus that belongs to the Flavivirus genus. After transmission of the virus occurs, it replicates in regional lymph nodes and subsequently spreads via the bloodstream. This widespread dissemination can affect the bone marrow, spleen, lymph nodes, kidneys, and liver, in addition to other organs. Tissue damage to the liver, for example, can lead to jaundice and disrupt the body's blood-clotting mechanism, leading to the hemorrhagic complications sometimes seen with yellow fever.

How is yellow fever transmitted?

Yellow fever is transmitted to humans by the bite of infected mosquitoes. Various species of Aedes and Haemagogus mosquitoes serve as vectors and are responsible for the transmission to human and nonhuman primates, which serve as reservoirs for the disease. Three transmission cycles for yellow fever have been identified.

  • Sylvatic (jungle) cycle: In tropical rainforests, infected monkeys pass the virus to mosquitoes that feed on them. These infected mosquitoes then bite humans who enter the rainforest for occupational (for example, loggers) or recreational activities.
  • Intermediate (savannah) cycle: In humid or semi-humid regions of Africa, mosquitoes that breed around households and in the wild (semi-domestic mosquitoes) infect both humans and monkeys. The virus can be transmitted from monkeys to humans, or from human to human by the mosquitoes. This is the most common type of outbreak in Africa.
  • Urban cycle: When infected humans introduce the virus into urban areas with large numbers of unvaccinated individuals, infected mosquitoes (Aedes aegypti) transmit the disease from human to human. This form of transmission can lead to large epidemics.
This picture shows a female Aedes aegypti mosquito.
This picture shows a female Aedes aegypti mosquito. Source: CDC

What areas are high risk for contracting yellow fever?

Yellow fever is endemic in tropical and subtropical regions of Africa and South America, though an estimated 90% of the cases reported occur in Africa. Most of the cases on the African continent occur in unvaccinated individuals who inhabit the sub-Saharan region. Though no cases of yellow fever outbreaks have ever been reported in Asia, this area remains a theoretical risk because the mosquitoes responsible for transmission, as well as the susceptible primates, are found there.

Countries where yellow fever is present
Source: CDC
AngolaGuyana
ArgentinaKenya
BeninLiberia
BoliviaMali
BrazilMauritania
Burkina FasoNiger
BurundiNigeria
CameroonPanama
Central African RepublicParaguay
ChadPeru
CongoRwanda
Congo, DRCSao Tome & Principe
ColombiaSenegal
Cote d'Ivoire (Ivory Coast)Sierra Leone
EcuadorSomalia
Equatorial GuineaSudan
EthiopiaSuriname
French GuianaTanzania
The GambiaTrinidad & Tobago
GabonTogo
GhanaUganda
GuineaVenezuela
Guinea-BissauZambia

Several factors determine an individual's risk of acquiring yellow fever during travel, including the area of travel, season, immunization status, duration of exposure, activities during travel, and the local rate of virus transmission. This information should be reviewed before any travel to endemic areas.

Picture of countries where yellow fever is present

Quick Guide25 Ways to Stay Well Abroad in Pictures

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What is the incubation period for yellow fever?

The period of time from contracting the infection to the development of symptoms (incubation period) is generally between three to six days.

Is yellow fever contagious? How long is the contagious period for yellow fever?

Yellow fever is transmitted to humans by the bite of infected mosquitoes. Yellow fever is not contracted by direct contact with other individuals who are infected. Humans with yellow fever are infectious and can transmit the virus to uninfected mosquitoes shortly before the onset of fever and for three to five days after the onset of symptoms.

What types of specialists treat yellow fever?

A variety of specialists may become involved in the care of patients who develop symptoms of yellow fever. Initially, primary-care physicians, including family physicians, internists, emergency physicians, and pediatricians, may encounter patients with yellow fever. When yellow fever is suspected or diagnosed, an infectious-disease specialist will likely be involved, as well. Depending on the severity of illness and the development of complications, other specialists may also be consulted (for example, a nephrologist in cases of kidney failure).

What are yellow fever symptoms and signs?

After infection with the yellow fever virus, many individuals will experience no clinically apparent manifestations of the disease (asymptomatic), while others will go on to develop a mild, self-limiting flu-like illness characterized by the following symptoms and signs:

Most patients with this initial acute phase of the disease improve spontaneously after approximately three to four days. However, approximately 15% of patients may enter a second phase of the disease which typically appears after a short remission of symptoms (about 24 hours) from the initial phase of the illness. This next toxic phase of the disease is more severe, at which time the high fever returns and more organ systems become involved. In addition to the above symptoms, the following symptoms and signs may also develop:

Quick Guide25 Ways to Stay Well Abroad in Pictures

25 Ways to Stay Well Abroad in Pictures

How do health-care professionals diagnose yellow fever?

Because the symptoms during the initial phase of yellow fever are nonspecific and similar to a flu-like illness, diagnosis during this stage can be difficult. Therefore, the preliminary diagnosis is often made clinically based on the patient's signs and symptoms, the travel history (when and where), and the related travel activities.

Various blood test abnormalities may be present in individuals with yellow fever, particularly those who go on to develop the second toxic phase of the disease. Blood test abnormalities may include a low white blood cell count (leukopenia), a low platelet count (thrombocytopenia), elevations in liver function tests, abnormally prolonged blood clotting times, and abnormal electrolyte and kidney function tests. None of these test results are specific to yellow fever and alone allow the health-care provider to make a diagnosis. Urine tests may demonstrate elevated levels of urinary protein and urobilinogen. An electrocardiogram (ECG) may reveal heart conduction or rhythm disturbances if cardiac involvement has occurred.

The laboratory diagnosis of yellow fever requires specialized testing. Blood tests may demonstrate the presence of virus-specific antibodies (IgM and IgG) produced in response to the infection, though cross-reactivity with antibodies from other flaviviruses may occur. Therefore, specific antibody testing, such as a plaque reduction neutralization test, may be done for confirmation.

What is the treatment for yellow fever?

There is no specific curative treatment for yellow fever. Treatment is supportive and aimed at relieving the symptoms of the disease, including the pain and fever. As previously mentioned, the majority of patients who do develop symptoms from yellow fever will experience a mild course of illness which will resolve on its own.

Supportive measures implemented depend on the severity of the disease, and may include

Acetylsalicylic acid (Aspirin) and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided because of the increased risk of bleeding.

For the first few days of illness, infected individuals should also be isolated indoors and/or under mosquito netting in order to prevent further mosquito exposure, thus eliminating the potential for further transmission of the disease.

How long does yellow fever last?

For individuals with yellow fever who develop the acute mild course of the illness, the symptoms will generally last about three to four days, and most patients will recover fully. For those individuals who develop the more serious toxic phase of the disease and survive, the course of the illness may last for several weeks depending on the severity of illness and any associated complications.

What is the prognosis for people with yellow fever?

The prognosis for individuals who develop uncomplicated yellow fever is generally excellent. However, for those patients who go on to develop the toxic phase of yellow fever, case-fatality rates range from 20%-50% depending on the underlying condition of the patient and the availability of supportive resources. If death occurs, it is typically within 10-14 days after the onset of the toxic phase. Infants and those older than 50 years of age tend to have more severe disease and higher mortality rates. Furthermore, host susceptibility and the virulence of the particular infecting strain can also influence mortality rates. In those individuals who survive yellow fever, generally there is no residual permanent organ damage.

Is it possible to prevent yellow fever?

Vaccination remains the most effective way of preventing yellow fever. The yellow fever vaccine has been used for several decades, and it is a safe vaccine with only rare serious adverse events reported. Since the undertaking of the Yellow Fever Initiative in 2006, visible progress in combating the disease has been made in West Africa with more than 105 million people receiving the vaccine in mass campaigns.

The yellow fever vaccine is a live virus vaccine that provides long-lasting immunity after a single dose. It provides immunity against yellow fever in 95% of individuals within one week of its administration. A booster dose is now not routinely recommended, except in very select cases. The vaccine is available for adults and children older than 9 months of age. It is recommended for travelers to areas where yellow fever is endemic and to local populations who are at risk. Several countries require travelers to demonstrate proof of yellow fever vaccination status for entry in order to prevent the importation and transmission of yellow fever. Check with a local health department for information regarding designated yellow fever vaccination centers.

Effective mosquito-control measures are also an important component for preventing or minimizing the risk of yellow fever. Avoiding mosquito bites by wearing protective clothing (long sleeves and long pants) and remaining in properly screened or air-conditioned accommodations is recommended. Furthermore, applying insect repellant containing DEET or picaridin on exposed skin is advised.

What are the side effects of the yellow fever vaccine?

The yellow fever vaccine can have rare but serious adverse side effects. It is generally administered in designated vaccination centers. Health-care providers need to consider the individual's underlying health, their risk of exposure to yellow fever, and the contraindications to vaccine administration before recommending it. To minimize the risk of serious adverse events, the Centers for Disease Control and Prevention (CDC) provides the following recommendations:

Contraindications (conditions in which the vaccine should not be given)

  • Allergy to vaccine component
  • Age <6 months
  • Symptomatic HIV infection or CD4+ T-lymphocytes <200/mm3 (<15% of total in children aged <6 years)
  • Thymus disorder associated with abnormal immune function
  • Primary immunodeficiencies
  • Malignant neoplasms
  • Transplantation
  • Immunosuppressive and immunomodulatory therapies

Precautions (conditions for which the risks of the vaccine and the disease should be carefully considered)

  • Age 6-8 months
  • Age ≥60 years
  • Asymptomatic HIV infection and CD4+ T-lymphocytes 200 to 499/mm3 (15%-24% of total in children aged <6 years)
  • Pregnancy
  • Breastfeeding

Individuals who do experience side effects from the yellow fever vaccine will generally experience mild symptoms, including low-grade fever, muscle aches, and headache. However, in rare cases, serious adverse events from the yellow fever vaccine can occur including life-threatening anaphylactic reactions, yellow fever vaccine-associated neurologic disease (a condition affecting the nervous system), and yellow fever vaccine-associated viscerotropic disease (a condition affecting the internal organs).

Where can people get more information on yellow fever?

"Yellow Fever," World Health Organization (WHO)

REFERENCES:

Switzerland. World Health Organization. "Media Centre: Yellow Fever." May 2016. <http://www.who.int/mediacentre/factsheets/fs100/en/>.

Switzerland. World Health Organization. "Yellow Fever." <http://www.who.int/topics/yellow_fever/en/>.

United States. Centers for Disease Control and Prevention. "Yellow Fever." July 12, 2016. <http://www.cdc.gov/yellowfever/index.html>.

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Reviewed on 9/30/2016
References
REFERENCES:

Switzerland. World Health Organization. "Media Centre: Yellow Fever." May 2016. <http://www.who.int/mediacentre/factsheets/fs100/en/>.

Switzerland. World Health Organization. "Yellow Fever." <http://www.who.int/topics/yellow_fever/en/>.

United States. Centers for Disease Control and Prevention. "Yellow Fever." July 12, 2016. <http://www.cdc.gov/yellowfever/index.html>.

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